Dockets Management Branch (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, Maryland 20852
Re: Docket No. 03D-0229, Federal Register: June 17, 2003 (Volume 68, Number 116, Page 35903)
The following comments are provided by the Biotechnology Industry Organization (BIO). BIO represents more than 1,000 biotechnology companies, academic institutions, state biotechnology centers and related organizations in all 50 U.S. states and 33 other nations. BIO members are involved in the research and development of health-care, agricultural, industrial and environmental biotechnology products. The Biotechnology Industry Organization (BIO) appreciates the opportunity to comment on the FDA's Guidance for Industry: Continuous Marketing Applications: Pilot 1 and 2.
These important pilots have the potential to improve communications between FDA and the sponsor, and to accelerate the review process. We believe such early review and feedback can lead to the identification and resolution of issues and deficiencies earlier in the process and look forward to their implementation.
BIO agrees that both the Pilot 1 and Pilot 2 CMA guidance documents are consistent with the PDUFA III goals letter. However, we request that FDA provide additional clarity in a few areas.
Pilot 1 (Reviewable Units, RU):
FDA prefers RUs to be the complete technical section, but they can also be defined subsets of the information for a discipline. Of the 6 defined disciplines, there are 11 different components that can potentially be RUs; some disciplines have sub-divisions that can be stand-alone RUs and some do not. The Chemistry, Manufacturing, and Controls section (CMC) is separated into Drug Substance and Drug Product, but only drug substance is defined as a RU. There is no further sub-division for CMC/Drug Product, and it would be useful and appropriate if there were. Some possibilities we suggest are: facilities, pharmaceutical development, validation, and stability.
FDA does not encourage CMC/Drug Product to be used as a RU due to the "impact on resource utilization". Nevertheless, if the sponsor has this information available, we believe that drug product information should explicitly be acceptable for early submission.
In the final guidance, please clarify whether a bundle of 2+ technical sections (i.e., two RU) submitted at the same time, such as CMC and Microbiology, would be considered one RU or two.
The guidance restricts the sponsor to submission of four RUs based on disciplines. However, it also provides some flexibility, allowing for deviations from the general recommendations outlined in the guidance at the discretion of the FDA review team. Please clarify if the recommendations outlined in the guidance are the minimum with regard to RU definitions, permitting a sponsor to submit more than four RUs.
Pilot 2 (Scientific Exchange and Communication):
We believe that a larger number of more diverse Pilot 2 products would yield better information on which to assess enhanced scientific exchange and communication. We are concerned that this may not occur for the following reasons:
The application for Pilot 2 must occur within a certain narrow window of product development. It is not clear that this will provide an adequate number of appropriate applications on which to judge the effectiveness of the concept. Therefore, we recommend that eligibility should include drugs that have received Fast Track designation and for which an IND has been filed, even if an end-of-phase 1 meeting has not been held.
Pilot 2 is specifically restricted to a relatively small number of applications (one per division). Fast Track applications are rare in some divisions, and not uncommon in others (e.g., oncology). As a result, the overall body of data collected on the concepts of scientific exchange and communication will be relatively small and may not adequately represent a cross-section of the U.S. pharmaceutical and biotech industries.
Please clarify in the final guidance whether the selected Pilot 2 products will be both Fast Track and Accelerated Approval, or if Pilot 2 designation will be independent of Accelerated Approval.
It is our understanding that FDA will evaluate the effectiveness of these programs by September 30, 2006, with a final report by September 30, 2007. Assuming that the programs are successful, we ask that the FDA consider increasing the number of Fast Track products per division covered by the Pilot 2 program.
BIO looks forward to the final guidance documents from the FDA on the CMA Pilot 1 and Pilot 2 programs. These programs will provide sponsors with more frequent and earlier feedback for Fast Track products, which will help ensure that innovative, effective and safe biological products continue to be developed to meet serious unmet medical needs.
Gillian R. Woollett, MA, DPhil
Vice President Science and Regulatory Affairs